Regulation of Cellular respiration and Related pathways

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Regulation of Cellular respirationandRelated
pathways
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Allosteric regulation Hexokinase is inhibited by
glucose-6-P. If glucose 6 phosphate accumulates
because the rate of glycolysis is low, then
hexokinase is inhibited and the conversion of
glucose to G6P slows. This is a very important
regulatory step, since it prevents the
consumption of too much cellular ATP to form G6P
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PFK is the valve controlling the rate of
glycolysis. -ATP inhibits the phosphofructokinase
reaction. AMP activates the reaction. Thus, when
energy is required, glycolysis is activated. When
energy is plentiful, the reaction is slowed down.
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• Phosphofructokinase is inhibited by citrate. A
  large number of compoundsfor example, fatty
  acids and amino acidscan be metabolized to TCA
  cycle intermediates. High concentrations of
  citrate indicate a plentiful supply of
  intermediates for energy production therefore,
  high activity of the glycolytic pathway is not
  required.
• This allows regulation between glycolysis and the
  Krebs cycle.

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-ATP inhibits pyruvate kinase similar to the
inhibition of PFK. -Pyruvate kinase is also
inhibited by acetyl-Coenzyme A. -Fatty acids
also allosterically inhibit pyruvate kinase,
serving as an indicator that alternative energy
sources are available for the cell.
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• Pyruvate kinase is also activated by
  fructose-1,6-bisphosphate. This is an example of
  feed-forward activation. If glycolysis is
  activated, then the activity of pyruvate kinase
  must also be increased in order to allow overall
  carbon flow through the pathway. Feed-forward
  activation ensures that the enzymes act together.

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Krebs cycle
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Pyruvate oxidation

• -Pyruvate dehydrogenase is allosterically
  inhibited by NADH and activated by high
  concentrations of NAD.
• -A high concentration of NADH in the cell means
  that the Electron Transport Chain is full of
  electrons and that ATP production is high.
• -Inhibition of this enzyme reduces the amount
  of Acetyl Co-A that enters into the Krebs cycle.
  

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• Citrate synthase is inhibited by ATP and NADH.
• Isocitrate dehydrogenase (ICDH) allosterically
  activated by ADP and NAD inhibited by ATP and
  NADH.
• Also, citrate accumulation and transport into the
  cytosol leads to activation of fatty acid
  biosynthesis (storage of acetyl-CoA as fat).

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Metabolic Pathways
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• Glucose is not the only fuel on which cells
  depend. Other carbohydrates, fats, even proteins
  may in certain cells or at certain times be used
  as a source of ATP.
• One of the great advantages of the step-by-step
  oxidation of glucose into CO2 and H2O is that
  several of the intermediate compounds formed in
  the process link glucose metabolism to the
  metabolism of other food molecules.

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• Fats are stored in adipose tissue.
• When needed as an energy source, the fat reserves
  are moved out of adipose tissue, and broken down
  into glycerol and fatty acids in the liver
• The glycerol portion of the molecule may be
  converted into DHAP and then to G3P and enters
  the glycolytic pathway.
• The glycerol may also be converted into glucose.
  This process is called gluconeogenesis.
• Fatty acids are converted into molecules of
  acetyl-CoA , in a process called b-oxidation, and
  are oxidized in the Krebs cycle of the
  mitochondria.

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• B oxidation involves the successive removal of
  two-carbon acetyl groups from the fatty acid.
  Each cleavage requires one ATP, but produces 1
  NADH and 1 FADH2.
• The result is that Palmitic Acid, a 16-carbon
  fatty acid, produces 131 ATP molecules, whereas 2
  glucose molecules produce 73 ATPs.
• By mass, lipids produce about twice the energy
  yield of carbohydrates

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• When fats are being used as the primary energy
  source such as in starvation, fasting or
  untreated diabetes, an excess amount of acetyl
  CoA is produced, and is converted into acetone
  and ketone bodies. This produces the sweet smell
  of acetone on the breath, noticeable in a
  diabetic state.

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• The amino acids liberated by the hydrolysis of
  proteins can also serve as fuel. First, the
  nitrogen is removed, a process called
  deamination. The remaining fragments then enter
  the respiratory pathway at several points.
• For example the amino acids Gly, Ser, Ala, and
  Cys are converted into pyruvic acid and enter the
  mitochondria to be respired.
• Acetyl-CoA and several intermediates in the
  Krebs cycle serve as entry points for most of
  the other amino acids.

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• These links permit the respiration of excess fats
  and proteins in the diet.
• No special mechanism of cellular respiration is
  needed by those animals that depend largely on
  ingested fats (e.g., many birds) or proteins
  (e.g., carnivores) for their energy supply.
• Many of the points that connect carbohydrate
  metabolism to the catabolism of fats and proteins
  serve as two-way valves. They provide points of
  entry not only for the catabolism (cellular
  respiration) of fatty acids, glycerol, and amino
  acids, but for their synthesis (anabolism) as
  well. Thus the catabolic breakdown of starches
  can lead (through acetyl-CoA and PGAL) to the
  synthesis of fat.